The October issue of Drug Discovery Today, Editor’s Choice features a series of articles with a focus on Biotherapeutics. I guess the field became energized some 40 years ago, with the pioneering work of Cesar Milstein at the NIMR, Mill Hill, London. It took some time, however, for the area to be ironed out and perhaps one of the major milestones in the public demonstration of this class of molecules to be effective therapies for disease was from the work of Tiny Maini and Marc Feldman of the Kennedy Institute of Rheumatology, using antibodies against TNFα to treat patients with rheumatoid arthritis. I do apologise for omissions here, I am sure that you all could name similar milestones in the development of antibodies in the therapy of disease, but this one is close to my heart and is the great grandfather of some of the best-selling antibody therapies of the current day. Biotherapeutics became the next big thing and this reputation was enhanced by technologies and approaches that addressed the issues related to this class of molecules. Soon the industry was buzzing with excitement at this new approach to treating disease. Moreover, it became clear that other biological molecules could also play a pivotal role as therapies, in particular (but not exclusively) nucleic acids. Biotherapeutics are now established as effective, generally safe therapies for a host of diseases and rightly occupy a central position in the arsenal of approaches that can be adopted by physicians, alongside the established small organic molecule therapies. In this newsletter, I have included 3 articles that give the state of play of biotherapeutics and some novel approaches to developing therapeutic agents going forward.

The first article of this month’s trilogy, is by Bilikallahalli K. Muralidhara, Rinku Baid, Steve M. Bishop, Min Huang, Wei Wang and Sandeep Nema, of Medimmune and Pfizer, USA entitled: “Critical considerations for developing nucleic acid macromolecule based drug products”. The article outlines how using nucleic acid macromolecules can represent a new paradigm in protein expression therapy, with great potential for the treatment of a wide variety of diseases. In particular, improvements in delivery, especially, non-viral, has allowed the targeting of diseases such as cancer, immunodeficiency disorders and infection via this approach. The issues with the use of therapies based upon the relatively labile nucleic acid structure relate more to the development of formulations intended to enhance stability during storage and to facilitate delivery. The review concisely covers the challenges and various strategies to achieve this end and details the various on-going clinical trials being performed with this class of molecules.

The second featured article, by Franziska Bootz and Dario Neri of Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zürich, Switzerland is entitled: “Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions”. The article covers antibody–cytokine fusion proteins, often referred to as immunocytokines. They combine the selectivity of antibodies with cytokine in order to fulfill a modulatory function with respect to immune response. At first, they were largely developed for applications related to the treatment of certain cancers whereas now, their potential to use anti-inflammatory cytokines in autoimmune and chronic inflammatory disorders is becoming more attractive. The review describes features germane to the design of immunocytokines and gives an overview of molecules in preclinical and clinical development.

Finally, is the article from Sophie Steeland, Roosmarijn E. Vandenbroucke and Claude Libert, of the University of Ghent, Belgium  entitled: “Nanobodies as therapeutics: big opportunities for small antibodies”. Previously known as the ship of the desert, camels (and other members of the Camelidae, including llamas) perhaps surprisingly offer some other benefits known to man, particularly those who live outside of the desert, or who are not interested in more esoteric forms of racing. That benefit is that the Camelidae, in addition to the production of conventional immunoglobulins, produce antibodies that lack light chains. The antigen-binding portion of these small antibodies are known as nanobodies. If judiciously chosen, nanobodies frequently exhibit better stability and reduced toxicity and immunogenicity to corresponding conventional antibodies. The authors discuss the applications of these molecules in medicine, in fields as diverse as oncology, inflammation, infections and neurological disorders. They also have potential as diagnostics and in imaging; the review finally discusses nanobodies that have been, or currently are undergoing clinical trials.  

Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents.